Last year, geneticists developed a new techniquethat allows them directly insert genes into bacterial DNA — or remove them. It was a powerful discovery, one that finally offered researchers a cheap and easy way to remove precise sections of a bacterial genome. And now, MIT researchers led by George Church have proven that the technique will also work in human cells — a confirmation that could transform the way genetic medicine is done, and introduce advanced therapies for genetic diseases, cancer, and AIDS.

According to the new study, two different developments allowed this to happen: zinc-finger nucleases and TALEN (Transcription Activator-Like Effector Nucleases) proteins. These techniques allow researchers to hone in on a particular part of a genome and snip the double-stranded DNA at a precise spot.

Researchers can use these methods to make two precise cuts to remove a piece of DNA and, if an alternative piece of DNA is supplied, the cell will plug it into the cut instead. In this way, doctors can excise a defective or mutated gene and replace it with a normal copy. Sangamo Biosciences, a clinical stage biospharmaceutical company, has already shown that replacing one specific gene in a person infected with HIV can make him or her resistant to AIDS.

Both the zinc finger and TALEN techniques require synthesizing a large new gene encoding a specific protein for each new site in the DNA that is to be changed. By contrast, the new technique uses a single protein that requires only a short RNA molecule to program it for site-specific DNA recognition, Doudna said.

In the new Science Express paper, Church compared the new technique, which involves an enzyme called Cas9, with the TALEN method for inserting a gene into a mammalian cell and found it five times more efficient.

"It (the Cas9-RNA complex) is easier to make than TALEN proteins, and it's smaller," making it easier to slip into cells and even to program hundreds of snips simultaneously, he said. The complex also has lower toxicity in mammalian cells than other techniques, he added.

"It's too early to declare total victory" over TALENs and zinc-fingers, Church said, "but it looks promising."